In this study, a new idea that electrogenic transporters determine cell resting state is presented. The previous assumption was that pumps, especially the sodium one, determine it. The latter meets ...difficulties, because it violates the law of conservation of energy; also a significant deficit of pump activity is reported. The amount of energy carried by a single ATP molecule reflects the potential of the inner mitochondrial membrane, which is about −200 mV. If pumps enforce a resting membrane potential that is more than twice smaller, then the majority of energy stored in ATP would be dissipated by each pump turning. However, this problem could be solved if control is transferred from pumps to something else, e.g., electrogenic transporters. Then pumps would transfer the energy to the ionic gradient without losses, while the cell surface membrane potential would be associated with the reversal potential of some electrogenic transporters. A minimal scheme of this type would include a sodium-calcium exchanger as well as sodium and calcium pumps. However, note that calcium channels and pumps are positioned along both intracellular organelles and the surface membrane. Therefore, the above-mentioned scheme would involve them as well as possible intercellular communications. Such schemes where various kinds of pumps are assumed to work in parallel may explain, to a great extent, the slow turning rate of the individual members. Interaction of pumps and transporters positioned at distant biological membranes with various forms of energy transfer between them may thus result in hypoxic/reperfusion injury, different kinds of muscle fatigue, and nerve-glia interactions.
The membrane transporters (pumps and co-transporters) are the main players in maintaining the cell homeostasis. Models of various types, each with their own drawbacks, describe transporter behavior. ...The aim of this study is to find the link between the biophysically based and empirical models to face and solve their specific problems. Instead of decreasing the number of states and using few complex rate constants as is usually done, we use the number of states as great as possible. Then, each transition in the cycle can represent an elementary process and we can apply the mass action law, according to which if rate constants depend on concentrations the dependence is linear. Thus, the expression for the steady state transporter current can be transformed from a function of rate constants into a function of concentrations. When transporter states form a single cycle, it can be characterized by two modes of action – forward and backward ones. Specific mode is realized depending on the available free energy. Each mode of action is characterized by a set of transporter affinities together with a parameter that describes the maximal turning rate. Except standard affinities corresponding to the substances that are binding to the transporter, affinities for the substances that are released are also defined. Such scheme provides great possibilities to construct approximations as each individual affinity could be estimated from experiments as precisely as possible. The approximations may be used for not only description and study of the transporter current but also in cellular models that attempt to describe wide variety of processes in excitable cells.
•General form of the steady state current valid for arbitrary transporter is proposed.•Expression for transporter current valid under very general assumptions is obtained.•Link between biophysically based and empirical models of pump is demonstrated.•A framework for expanding complexity of empirical models is proposed.
The use of additive manufacturing to produce intricate part geometries in the aerospace, medical, and tool-and-die industries is increasingly incorporated in manufacturing process chains. However, ...the high costs, long production times, and material integrity issues associated with additive manufacturing technologies such as selective laser melting make the process suitable only for certain applications. In order to reduce selective laser melting production costs for selected parts, a combination of selective laser melting and milling can be used. Metal parts produced with this method are referred to as hybrid parts. A challenge in producing hybrid parts is to reduce the geometrical deviation due to process-induced warping. This paper discusses the effects of various laser scan strategies on the deviation of hybrid parts. A newly developed scan strategy is experimentally compared with its commercial counterpart with regard to as-built part warping and porosity. The novel strategy resulted in a significant reduction in warping and porosity.
The objective of machining performance is to reduce operational costs and to increase the production rate while maintaining or improving the required surface integrity of the machined component. ...Together with industrial partners, several benchmark titanium components were selected and machined to achieve this. Titanium alloys are used extensively in several industries due to its unique strength-to-weight ratio and corrosion resistance. Its properties, however, also make it susceptible to surface integrity damage during machining operations. The research objectives of this study were to understand the effect of cutting parameters on surface integrity to ensure that machined components are within the required surface quality tolerances. The effect of cutting speed and feed rate on surface roughness, micro-hardness, and the microstructure of the work piece were studied for milling Ti6Al4V. The surface roughness increased with a greater feed rate and a decrease in cutting speed. The maximum micro-hardness was 23 per cent harder than the bulk material. Plastic deformation and grain rotation below the machined surface were found with the rotation of the grain lines in the direction of feed. There was no evidence of subsurface defects for any of the cutting conditions tested.
To compare the efficacy of leucovorin-modulated fluorouracil (FU+LV) with that of fluorouracil and levamisole (FU+LEV) or with the combination of FU+LV and levamisole (FU+LV+LEV).
Between July 1989 ...and December 1990, 2,151 patients with Dukes' B (stage II) and Dukes' C (stage III) carcinoma of the colon were entered onto National Surgical Adjuvant Breast and Bowl Project protocol C-04. Patients were randomly assigned to receive FU+LV (weekly regimen), FU + LEV, or the combination of FU+LV+LEV. The average time on study was 86 months.
A pairwise comparison between patients treated with FU+LV or FU+LEV disclosed a prolongation in disease-free survival (DFS) in favor of the FU+LV group (65% v 60%; P =.04); there was a small prolongation in overall survival that was of borderline significance (74% v 70%; P =.07). There was no difference in the pairwise comparison between patients who received FU+LV or FU+LV+LEV for either DFS (65% v 64%; P =.67) or overall survival (74% v 73%; P =.99). There was no interaction between Dukes' stage and the effect of treatment.
In patients with Dukes' B and C carcinoma of the colon, treatment with FU+LV seems to confer a small DFS advantage and a borderline prolongation in overall survival when compared with treatment with FU+LEV. The addition of LEV to FU+LV does not provide any additional benefit over and above that achieved with FU+LV. These findings support the use of adjuvant FU+LV as an acceptable therapeutic standard in patients with Dukes' B and C carcinoma of the colon.
This paper investigates the behavior of titanium formability when forming under localized friction heating, caused by high tool rotation. In accordance with planned experiments, different process ...conditions at various tool rotations, feed rates, and step-down sizes were investigated. The experiments were carried out on 1 mm thick Ti6Al4V alloy sheets, using an 11 mm diameter, ball-ended tooltip. The rotational speeds were designed to create sufficient thermal effect, while maintaining high lubricity at the forming interface. Moderate tool rotational speed (2000 rpm) tends to improve formability, reduce the forces, and lower the rate of tool wear. The experimental procedures are presented, and an extensive discussion of the results is reported.
The effects of tool rotation direction during single point incremental forming of pure titanium were experimentally studied. Axisymmetric components with a varying wall angle were formed using a ...round-tipped tool of 10 mm diameter and following a 3D spiral tool path. Test runs were executed by changing one factor at a time. Spindle rotation was tested in both the climb and the conventional directions. Tool step depth between runs was increased by a fixed interval over the range of 0.35 mm up to the plate thickness of 0.8 mm. The experimental results obtained by a comparison between the two forming strategies and their impact on the characteristics of formability are discussed in this paper. The achieved level of the forming angle (75
°
), and the reduction in geometric deviations from the conventional strategy, presents interesting findings. Considerable variations in the trends of forces and temperature between the two forming strategies are presented and discussed.
This paper reveals the main problems of creating and implementing double diploma programs between universities of Russia and Europe. Novosibirsk State Technical University implements such programs ...with Technical Universities of Sofia (Bulgaria) and Liberec (Czech Republic). The paper presents the latest results of this activity and discusses the possibilities of its development in the field of joint postgraduate training, as well as joint scientific research with the involvement of students and postgraduate.
Abstract Parathyroid hormone receptor 2 (PTH2R) and its ligand, tuberoinfundibular peptide of 39 residues (TIP39) constitute a neuromodulator system implicated in endocrine and nociceptive ...regulation. We now describe the presence and distribution of the PTH2R and TIP39 in the brain of primates using a range of tissues and ages from macaque and human brain. In situ hybridization histochemistry of TIP39 mRNA, studied in young macaque brain, due to its possible decline beyond late postnatal ages, was present only in the thalamic subparafascicular area and the pontine medial paralemniscal nucleus. In contrast, in situ hybridization histochemistry in macaque identified high levels of PTH2R expression in the central amygdaloid nucleus, medial preoptic area, hypothalamic paraventricular and periventricular nuclei, medial geniculate, and the pontine tegmentum. PTH2R mRNA was also detected in several human brain areas by RT-PCR. The distribution of PTH2R-immunoreactive fibers in human, determined by immunocytochemistry, was similar to that in rodents, including dense fiber networks in the medial preoptic area, hypothalamic paraventricular, periventricular and infundibular (arcuate) nuclei, lateral hypothalamic area, median eminence, thalamic paraventricular nucleus, periaqueductal gray, lateral parabrachial nucleus, nucleus of the solitary tract, sensory trigeminal nuclei, medullary dorsal reticular nucleus, and dorsal horn of the spinal cord. Co-localization suggested that PTH2R fibers are glutamatergic, and that TIP39 may directly influence hypophysiotropic somatostatin containing and indirectly influence corticotropin releasing-hormone containing neurons. The results demonstrate that TIP39 and the PTH2R are expressed in the brain of primates in locations that suggest involvement in regulation of fear, anxiety, reproductive behaviors, release of pituitary hormones, and nociception.
Geological methane, generated by microbial decay and the thermogenic breakdown of organic matter, migrates towards the surface (seabed) to be trapped in reservoirs, sequestered by gas hydrates or ...escape through natural gas seeps or mud volcanoes (via ebullition). The total annual geological contribution to the atmosphere is estimated as 16–40 Terragrammes (Tg) methane; much of this natural flux is ‘fossil’ in origin. Emissions are affected by surface conditions (particularly the extent of ice sheets and permafrost), eustatic sea‐level and ocean bottom‐water temperatures. However, the different reservoirs and pathways are affected in different ways. Consequently, geological sources provide both positive and negative feedback to global warming and global cooling. Gas hydrates are not the only geological contributors to feedback. It is suggested that, together, these geological sources and reservoirs influence the direction and speed of global climate change, and constrain the extremes of climate.
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